Exendin-4, a GLP-1 receptor agonist, modulates the effect of macronutrients on food intake by rats.

The hypothesis that peripheral GLP-1 modulates the effect of macronutrients on food intake in rats was tested by administration of its agonist, exendin-4. The effect of exendin-4 on food intake suppression and blood glucose after carbohydrate, fat and protein preloads was measured. Exendin-4 reduced the effect of glucose preloads on food intake only during the first 30 min (P = 0.01) of feeding, but had a more prolonged effect when given with corn oil (P < 0.01 at 0-0.5 h and 0-1 h, P = 0.055 at 0-2 h, and P = 0.07 at 0-3 h) and whey (P < 0.05 at 0-1 h, P = 0.06 at 0-2 h, and P = 0.07 at 0-3 h) preloads. Blood glucose measured over 2 h was reduced at 15 min when given with glucose (P < 0.01), unchanged when given with corn oil and increased at 60 and 120 min when given with whey (P < 0.01). Thus, the effect of exendin-4 on the feeding response depended on the composition of the macronutrient preloads and seems to be independent of blood glucose concentrations.